Colonoscopy with removal of any polyps discovered during the procedure is used widely to reduce the risk of developing colorectal cancer. Life-threatening complications of polypectomy include perforation and bleeding. Delayed (occurring at some point after completion of the colonoscopy) post-polypectomy bleeding can result in hospitalization, blood transfusion, and repeat colonoscopies to treat the bleeding site. Increased risk for post-polypectomy bleeding has been associated with the removal of large polyps, sessile polyps, and pedunculated polyps that have a thick stalk. Use of anticoagulants and co-morbid conditions such as diabetes, coronary disease, lung disease, and renal disease also are associated with an increased risk for post-polypectomy bleeding. It is now a common clinical practice for colonoscopists to place hemoclips (metal clips passed through the colonoscope to close defects in the colon mucosa) prophylactically after polypectomy, particularly after the removal of large polyps, in an attempt to prevent delayed post-polypectomy bleeding. However, few published data support this expensive practice, and there are no clear guidelines on when or how to perform prophylactic hemoclipping. When performing prophylactic hemoclipping, furthermore, colonoscopists commonly apply multiple clips to each polypectomy site. At a cost of $150 per clip, this practice can dramatically increase the cost of colonoscopy. At our VA Medical Center alone, we spend approximately $64,000 per year on hemoclips applied prophylactically. Despite the widespread clinical practice of prophylactic hemoclipping, only one randomized trial has evaluated its efficacy. Although the investigators found no significant difference in post- polypectomy bleeding rates between patients who had hemoclips placed prophylactically and those who did not, this study has been criticized because most of the polyps removed were small. The average size of those polyps was only 7 mm, and patients with polyps >3 cm were excluded. Such small polyps are unlikely to bleed, and are not routinely hemoclipped in clinical practice. Thus, the efficacy of the common, expensive practice of prophylactic hemoclipping of large polypectomy sites remains unknown. The goal of this study is to determine whether the prophylactic placement of hemoclips at the polypectomy site after the removal of large polyps (e1cm in size) will reduce the rate of clinically important delayed post-polypectomy bleeding. We hypothesize that this prophylactic placement of hemoclips does not decrease the risk of such bleeding. In order to test this hypothesis, we plan for a prospective, randomized equivalence study of clipping versus no clipping after large (e1cm) polyp removal. We plan to enroll 1622 patients (811 into each arm) into the study. We will include patients on anti-platelet agents and anticoagulation. Our primary end point will be to determine the frequency of clinically-important, delayed post-polypectomy bleeding (defined as bleeding within 30 days of polypectomy that results in blood transfusion, hemodynamic instability, or a drop in blood hemoglobin level of >2 grams per deciliter) between groups of patients who had polypectomy performed with and without prophylactic hemoclipping. Subgroup analyses based on anticoagulant use and polyp characteristics will be performed.